Phenmetrazine

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Phenmetrazine
Phenmetrazine.svg
Systematic (IUPAC) name
3-methyl-2-phenylmorpholine
Clinical data
Legal status Schedule IV (CA) Class B (UK) Schedule II (US)
Routes Oral, Intravenous, Vaporized, Insufflated, Suppository
Pharmacokinetic data
Half-life 8 hours
Excretion Renal
Identifiers
CAS number 134-49-6 YesY
ATC code None
PubChem CID 4762
DrugBank DB00830
ChemSpider 4598 YesY
UNII XA501VL3VR YesY
KEGG C07432 YesY
ChEMBL CHEMBL1201208 N
Chemical data
Formula C11H15NO 
Mol. mass 177.2456
 N (what is this?)  (verify)

Phenmetrazine (Preludin, PAL-592) is a stimulant drug containing a phenethylamine skeleton, in which the terminal amine is incorporated into a morpholine ring, that was previously used as an appetite suppressant, but has since been withdrawn from the market. It was initially replaced by its analogue phendimetrazine which functions as a prodrug to phenmetrazine, but now it is rarely prescribed, due to concerns of abuse and addiction.

History[edit]

Phenmetrazine was first patented in Germany in 1952 by Boehringer-Ingelheim,[1][2] with some pharmacological data published in 1954.[3] It was the result of a search by Thomä and Wick for an anorectic drug without the side-effects of amphetamine.[4] Phenmetrazine was introduced into clinical use in 1954 in Europe.[5]

Medical use[edit]

In clinical use, phenmetrazine produces less nervousness, hyperexcitability, euphoria and insomnia than drugs of the amphetamine family.[6] It tends not to increase heart rate as much as other stimulants. Due to the relative lack of side effects, one study found it well tolerated in children.[4] In a study of the effectiveness on weight loss between phenmetrazine and dextroamphetamine, phenmetrazine was found to be slightly more effective.[7]

Pharmacology[edit]

Phenmetrazine acts as a releasing agent of norepinephrine and dopamine with EC50 values of 50.4 ± 5.4 nM and 131 ± 11 nM, respectively.[8] It has negligible efficacy as a releaser of serotonin, with an EC50 value of only 7,765 ± 610 nM.[8]

After an oral dose, about 70% of the drug is excreted from the body within 24 hours. About 19% of that is excreted as the unmetabolised drug and the rest as various metabolites.[9]

In trials performed on rats, it has been found that after subcutaneous administration of phenmetrazine, both optical isomers are equally effective in reducing food intake, but in oral administration the levo isomer is more effective. In terms of central stimulation however, the dextro isomer is about 4 times as effective in both methods of administration.[10]

Its structure incorporates the backbone of amphetamine, the prototypical CNS stimulant which, like phenmetrazine, is a releasing agent of dopamine and norepinephrine. The molecule also loosely resembles ethcathinone, the active metabolite of popular anorectic amfepramone (diethylpropion). Unlike phenmetrazine, ethcathinone (and therefore amfepramone as well) are mostly selective as noradrenaline releasing agents.

Recreational use[edit]

Phenmetrazine has been used recreationally in many countries, for example Sweden. When stimulant use first became prevalent in Sweden in the 1950s, phenmetrazine was preferred to amphetamine and methamphetamine by users.[11] In the autobiographical novel "Rush" by Kim Wozencraft, intravenous phenmetrazine is described as the most euphoric and pro-sexual of the stimulants the author used.

Phenmetrazine was classified as a narcotic in Sweden in 1959, and was taken completely off the market in 1965. At first the illegal demand was satisfied by smuggling from Germany, and later Spain and Italy. At first, Preludin tablets were smuggled, but soon the smugglers started bringing in raw phenmetrazine powder. Eventually amphetamine became the dominant stimulant of abuse because of its greater availability.

Phenmetrazine was taken by The Beatles early in their career. Paul McCartney was one known user. McCartney's introduction to drugs started in Hamburg, Germany. The Beatles had to play for hours, and they were often given "Prellies" (Preludin) by the maid who cleaned their housing arrangements, German customers, or by Astrid Kirchherr (whose mother bought them). McCartney would usually take one, but John Lennon would often take four or five.[12] Hunter Davies asserted, in his 1968 biography of the band,[13] that their use of such stimulants then was in response to their need to stay awake and keep working, rather than a simple desire for kicks.

Jack Ruby said he was on phenmetrazine at the time he killed Lee Harvey Oswald.[14]

Preludin was also used recreationally in the U.S.A. throughout the 1960s and early 1970s. It could be crushed up in water, heated and injected. The street name for the drug in Washington, D.C. was "Bam".[15] More recently phenmetrazine has continued to be abused around the world, in countries such as South Korea.[16]

See also[edit]

References[edit]

  1. ^ Albert Boehringer; Ernst Boehringer. Improvements in or relating to the preparation of substituted morpholines. GB773780.
  2. ^ US Patent 2835669 - Process for the Production of Substituted Morpholines
  3. ^ Thomä, O and Wick, H (1954). "Über einige Tetrahydro-1,4-oxazine mit sympathicomimetischen Eigenschaften". Arch. Exp. Path. Pharm 222: 540. 
  4. ^ a b Martel, Antonio (1957). "Preludin (Phenmetrazine) in the Treatment of Obesity". Can. Med. Assoc. J. 76 (2): 117–20. PMC 1823494. PMID 13383418. 
  5. ^ Kalant, Oriana Josseau (1966). The Amphetamines: Toxicity and Addiction. ISBN 0-398-02511-8. 
  6. ^ "Phenmetrazine Hydrochloride". J. Am. Med. Assoc. 163 (5): 357. 1957. 
  7. ^ Hampson, J; Loraine, J.A.; Strong, J.A. (1960). "Phenmetrazine and Dexamphetamine in the Management of Obesity". The Lancet 275 (7137): 1265–7. doi:10.1016/S0140-6736(60)92250-9. PMID 14399386. 
  8. ^ a b Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry 6 (17): 1845–59. doi:10.2174/156802606778249766. PMID 17017961. 
  9. ^ Anthony C Moffat, M David Osselton and Brian Widdop. Clarke's Analysis of Drugs and Poisons. ISBN 0-85369-473-7. 
  10. ^ Engelhardt, A (1961). "Studies of the Mechanism of the Anti-Appetite Action of Phenmetrazine". Biochem. Pharmacol. 8 (1): 100. doi:10.1016/0006-2952(61)90520-2. 
  11. ^ Brecher, Edward M. "The Swedish Experience". Retrieved 2009-10-31. 
  12. ^ Miles, Barry (1998). Paul McCartney: Many Years from Now. pp. 66–67. ISBN 0-8050-5248-8. 
  13. ^ Davies, Hunter (1968). The Beatles: The Authorized Biography. p. 78. ISBN 0-07-015457-0. 
  14. ^ Testimony of Jack Ruby 5. Washington: Government Printing Office. 1964. pp. 198–99.
  15. ^ Leon Dash (1996). Rosa Lee. HarperCollins. p. 109. 
  16. ^ Choi H, Baeck S, Jang M, Lee S, Choi H, Chung H (10 February 2012). "Simultaneous analysis of psychotropic phenylalkylamines in oral fluid by GC-MS with automated SPE and its application to legal cases". Forensic Science International 215 (1–3): 81–87. PMID 21377815.